The present proposal constitutes a longitudinal evaluation of subjects already assessed and treated acutely, in some cases, already maintained on medication (AMI or DMI) as long as 6 months. By the start of this project, we will have gathered a patient cohort (n=100) which will have been treated for at least 6 weeks on DMI or AMI. We expect 70 to respond and enter our 6 month drug maintenance phase. Forty will survive the drug taper and enter our subsequent 12-month single-blind placebo followup period. We will evaluate these subjects monthly with DST, sleep EEG, cognitive, and clinical measures. This study was designed to (1) determine the order in which biologic and cognitive abnormalities develop in relation to the onset of clinical exacerbation or relapse; (2) identify which biologic or psychologic abnormalities are, antecedents, concomitants, or consequences of clinical depression; (3) evaluate the clinical value of these biologic and psychologic measures in predicting clinical relapse or persistent moderate symptomatology, and (4) assess whether prognostication based on these measures exceeds those derived from clinical and illness history variables.